Systemic Lupus Erythematosus

Malar rash on a patient with systemic lupus erythematosus.

Signs and Symptoms: Systemic lupus erythematosus (SLE) commonly presents in young and middle-aged women, who comprise up to 90% of all SLE sufferers.^1-7 SLE is three times more common in blacks than in other races, and Asians display an increased incidence of SLE vs. Caucasians.^1,2,4

Patients suffer chronic relapses and an unpredictable course secondary to a hyperactive immune system and excessive autoantibody production. Because lupus affects many organ systems, it creates a diverse clinical picture including erythematosus rash, polyarthralgia and arthritis, anemia, and cardiac, renal and neurologic abnormalities. Renal failure is a major cause of death in those suffering from severe, chronic SLE.

The skin changes associated with SLE are described as a butterfly rash, often the primary manifestation of SLE. Ocular manifestations, which occur in up to 20% of SLE patients,^1-4 also may be the initial presenting sign, and may precede systemic signs or symptoms by several months.

Discoid lupus erythematosus presents with eyelid erythema and atrophic plaques, often accompanied by loss of skin pigment, loss of eyelashes, dilated dermal vessels and cellular infiltrates. If untreated, the lids become scarred. Infiltration of the lacrimal gland may cause proptosis.

Keratitis sicca occurs in many SLE patients, leading to corneal exposure, stromal infiltrates, marginal infiltrates, pannus formation and, ultimately, ulceration. Rare corneal manifestations include neovascularization, deep interstitial keratitis and kerato-endothelitis.

Other ocular signs include migraine headache, uveitis, diffuse or nodular scleritis, vitreoretinal and choroidal inflammation, subretinal neovascular membrane formation, retinal vascular occlusion and neuro-ophthalmic sequelae. Multiple cotton-wool spots are a common retinopathy.

Pathophysiology: A genetic predisposition has been implicated in SLE, as well as environmental factors. Procainamide and hydrazaline may increase immune activity or decrease immune suppressor function.

In the eye, immune complex deposits in the vascular endothelium of the conjunctiva, sclera, choroid, ciliary body and retina alter the tissue structure and compromise function. Deposits can also develop in the basement membrane of the ciliary body, cornea and along the peripheral nerves of the ciliary body and conjunctiva.

While most patients with retinopathy have systemic disease, retinopathy can also occur independently of systemic flare-ups. SLE patients with retinopathy have a higher morbidity risk.

Management: There is no known cure for SLE, and complete remission rarely occurs.

Clinicians use four drug classes to manage these patients: salicylates/NSAIDS, antimalarials, corticosteroids and cytotoxic agents. Salicylates and NSAIDS are useful in treating arthralgias, arthritis, myalgias and fever in those without life-threatening manifestations.

Therapy for the ocular manifestations is based on successful systemic control. Systemic corticosteroids used for two or more years may lead to cataracts or glaucoma. Monitor these patients every 3-6 months.

Plaquenil (hydroxychloroquine, Sanofi) 200mg qd may cause a reversible corneal edema and whorl-like pigmentary deposits in the epithelium. After 2-3 years of therapy, patients may also develop bull's-eye maculopathy. Monitor patients every six months for changes in visual acuity, color vision and central and peripheral fields. If retinopathy occurs, discontinue drug therapy.

Systemic and topical corticosteroids and hydroxychloroquine are useful in treating eyelid plaques. Immunosuppressive agents can relieve secondary proptosis. Systemic and topical corticosteroids will decrease corneal inflammation. Artificial tears and ointments or punctal plugs will decrease dryness. Antibiotics may treat infections or to prevent ulceration.

Resolution of scleritis and choroiditis requires adequate control of the systemic disease. Anticoagulant therapy is indicated if the disease is associated with antiphospholipid antibodies. Topical steroid drops and cycloplegics will treat any associated uveitis.

Retinopathy may greatly improve following treatment of the systemic disease; however, you must monitor the patient carefully for exacerbations in the absence of systemic signs. Antiplatelet and anticoagulant therapy is indicated for occlusive retinopathy. Nifedipine therapy may be useful for both the migraines and the amaurosis seen in SLE. Systemic steroids are indicated to reverse painful ophthalmoplegia.

Clinical Pearls

• SLE patients with chronic eyelid lesions are sometimes misdiagnosed as having eczema or infectious blepharitis. Sarcoidosis, psoriasis, verrucae, trachoma and syphilis may also present with similar signs and symptoms
• SLE retinopathy can mimic hypertension or diabetic retinopathy, but is associated with less ischemia and visual loss. Hard exudates, cotton-wool spots, arteriole narrowing, A/V crossing changes, macular pigmentary mottling and retinal scarring can occur in one or both eyes. SLE retinal vascular occlusive disease may also present with bilateral mottled retinas and pigment spots resembling retinitis pigmentosa.
• Multiple sclerosis may be mistaken for SLE because of the neurological manifestations and the mode of presentation.
• Lifestyle changes including rest and decreased stress, use of sunscreen and avoidance of ultraviolet light can minimize disease episodes. Monitor patients for possible ocular side effects of systemic treatment.
• An unusually high number of cotton wool-spots increases suspicion of SLE.

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2. Nguyen QD, Foster CS. Systemic lupus erythematosus and the eye. Int Ophthalmol Clin 1998;38(1):33-60.
3. Bouchard CS, Melton JL. Lupus Erythematosus. In: Mannis MJ, Macsai MS, Huntley AC, eds. Eye and Skin Disease. Philadelphia: Lippincott-Raven Publishers. 1996:177-184.
4. Hakin KN, Lightman S. Systemic Lupus Erythematosus. In: Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease. New York: Marcel Dekker Inc. 1994:197-199.
5. Green WR. Retina. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook. Philadelphia: W. B. Saunders 1996:1130-1131.
6. Jensen JL, Bergem HO, Gilboe IM, et al. Oral and ocular sicca symptoms and findings are prevalent in systemic lupus erythematosus. J Oral Path Med 1999;28(7):317-322.
7. Mehta AM, France TD. Prominent ocular findings as an early manife station of systemic lupus erythematosus. J Ped Ophthalmol Strabismus 1998;35(2):114-115.